Antidepressant-like effect of triterpenoids extracts from Poria cocos on the CUMS rats by 16S rRNA gene sequencing and LC–MS metabolomics

Abstract

Poria cocos is an edible medicinal mushroom with the effects of inducing diuresis, excreting dampness, invigorating the spleen and tranquilizing the mind. The triterpenoids of Poria cocos as the main active ingredients have shown health benefits of the central nervous system of the human body. Accordingly, this study aimed at further understanding the antidepressant-like effect and a potential mechanism of the triterpenoids extracts from Poria cocos (TPC). As a result, the TPC significantly ameliorated depression-like behaviors on chronic unpredictable mild stress (CUMS) rats, and restored the levels of brain-derived neurotrophic factor and nerve growth factor in the hippocampus of rats. Gut microiota analysis revealed that TPC could increase the biodiversity and markedly regulate the relative abundance of [Prevotella], Allobaculum and Ochrobactrum of CUMS rats. The cecal contents metabolomics pointed to thirteen biomarkers associated with TPC antidepressant effect, which involved in primary bile acid biosynthesis, taurine and hypotaurine metabolism, arginine and proline metabolism. Correlation analysis further showed that there was a strong correlation relationship between the gut microbiota and the cecal contents metabolites, especially compounds involved in energy metabolism, inflammation and immunity. In conclusion, TPC showed a potential antidepressant effect, which was possibly mediated the gut microbiota and cecal contents metabolism.     

Submicron carbon-based hybrid nano-pour-point depressant with outstanding pour point depressant and excellent viscosity depressant

We have investigated the effective utilization potential of carbon nanomaterials in the field of pour point depressants, and reported three kind of carbon-based hybrid nano-pour-point depressants with different dimensions. In this paper, poly-α-olefins-acrylate high-carbon ester pour point depressant (PAA-18) was prepared by esterification and polymerization as the basic pour point depressant. Then, the basic pour point depressant PAA18 was modified by solvothermal method with graphene oxide (GO), carbon nanospheres (Cna) and carbon nanotubes (OCNTs). The morphology and structure of the composites were analyzed by SEM, FTIR and XRD. The results showed that PAA18 was successfully in situ polymerized on GO, Cna and OCNTs. We took the simulated oil as the experimental object, and evaluated its pour point, rheological properties and wax crystal morphology, and achieved excellent results. In the three carbon-based hybrid nano-pour-point depressants with different carbon contents, the oxidation carbon nanotubes composite pour point depressant (PAA18-1 % OCNTs) with carbon content of 1 % had the best pour point and viscosity reduction effect when the dosage was 1250 ppm, which could make the pour point of the simulated oil containing wax decrease by 16 °C. PAA18-1 % OCNTs reduced the pour point by 5 °C more than PAA18. This paper provides reference for the application of carbon nanomaterials in the field of pour point depressant.     

Prediction of 5-hydroxytryptamine transporter inhibitors based on machine learning

In patients with depression, the use of 5-HT reuptake inhibitors can improve the condition. Machine learning methods can be used in ligand-based activity prediction processes. In order to predict SERT inhibitors, the SERT inhibitor data from the ChEMBL database was screened and pre-processed. Then 4 machine learning methods (LR, SVM, RF, and KNN) and 4 molecular fingerprints (CDK, Graph, MACCS, and PubChem) were used to build 16 prediction models. The top 5 models of accuracy (Q) in the cross-validation of training set were used to build three different ensemble learning models. In the test1 set, the VOT_CLF3 model had the largest SP (0.871), Q (0.869), AUC (0.919), and MCC (0.728). In the unbalanced test2 set, VOT_CLF3 had the largest SE (0.857), SP (0.867), Q (0.865) and MCC (0.639). VOT_CLF3 was recommended for the virtual screening process of SERT inhibitors. In addition, 12 molecular structural alerts that frequently appear in SERT inhibitors were found (P < 0.05), which provided important reference value for the design work of SERT inhibitors.     

Analysis of signal fluctuations of Cortical Spreading Depression: Preliminary findings

In this work, we apply Detrended Fluctuation Analysis (DFA) to study the dynamics of electrical cortical activity in rats during the phenomenon of Cortical Spreading Depression (CSD), as well as the periods before and after this phenomenon. The characteristic of CSD is reduced electrical activity that occurs and spreads in the cerebral cortex after the application of electrical, chemical or mechanical stimulus. Our results show that the electrocorticogram signal shows long range temporal correlations and scaling behavior, except during the pre-CSD burst phase (significant increase of amplitude provoked by stimulus).     

丁螺环酮联合草酸艾司西酞普兰 治疗抑郁症的增效作用和安全性 观察

目的 探讨丁螺环酮联合草酸艾司西酞普兰治疗抑郁症的增效作用和安全性。方法 选取符合ICD-10 抑郁发作 诊断标准,经草酸艾司西酞普兰足量（20mg/d）、足疗程（6周）治疗未获得痊愈的45 例抑郁症患者,加用丁螺环酮15~60mg/d,观察8周,并分别在治疗前、治疗后第1、4、8周末分别评估汉密尔顿抑郁量表（HAMD）和汉密尔顿焦虑量表（HAMA）,以第1周末HAMA 评分≤7分为界,分为焦虑控制组（HAMA 评分≤7 分）和焦虑未控制组（HAMA 评分＞7 分）;以8周末HAMD≤7分为标准,分为获得痊愈组（HAMD≤7 分）和未获得痊愈组（HAMD＞7 分）;并在治疗第1、4、8周末分别评估不良反应。结果 在治疗第4周,获得痊愈20 例（44.4%）,第8 周末获得痊愈25 例（55.5%）。治疗后第4、8 周,获得痊愈组的患者HAMA 评分明显低于未获得痊愈组（P＜0.05）。治疗后第1、4周,焦虑控制组和焦虑未控制组患者HAMD 评分比较差异无统计学意义,治疗后第8 周,两组患者HAMD 评分 比较差异有统计学意义（P＜0.05）。不良反应以口干（40.0%）、便秘（36.9%）及乏力（13.3%）为多见。结论 经草酸艾司西酞普兰足量、足疗程治疗后仍未彻底痊愈的患者加用丁螺环酮可进一步获得疗效,提高痊愈率,安全性良好。     

Free surface flow under gravity and surface tension due to an applied pressure distribution: I Bond number greater than one-third

We consider steady free surface two-dimensional flow due to a localized applied pressure distribution under the effects of both gravity and surface tension in water of constant depth, and in the presence of a uniform stream. The fluid is assumed to be inviscid and incompressible, and the flow is irrotational. The behavior of the forced nonlinear waves is characterized by three parameters: the Froude number, F, the Bond number, τ > 1/3, and the magnitude and sign of the pressure forcing parameter ɛ. The fully nonlinear wave problem is solved numerically by using a boundary integral method. For small amplitude waves and F < 1 but not too close to 1, linear theory gives a good prediction for the numerical solution of the nonlinear problem in the case of bifurcation from the uniform flow. As F approaches 1, the nonlinear terms need to be taken account of. In this case the forced Korteweg-de Vries equation is found to be an appropriate model to describe bifurcations from an unforced solitary wave. In general, it is found that for given values of F < 1 and τ > 1/3, there exists both elevation and depression waves. In some cases, a limiting configuration in the form of a trapped bubble occurs in the depression wave solutions.     

Antidepressant-like effect of Casimiroa pubescens root extracts

In this study, we investigated the antidepressant-like effects of the hexane (HCP), ethyl acetate (ECP) and methanol (MCP) extracts of the roots of Casimiroa pubescens Ramírez (Rutaceae) using the forced swim test (FST). In an initial experiment, each extract was orally administered to mice only once 60 min before to the FST. In a second experiment, doses were administered 24, 7 and 1 h before testing. Our results showed that the triple administration of the extracts provided a stronger effect than single administration. However, the combination of HCP at 7.5 mg/kg and imipramine (IMI) at 12.5 mg/kg showed the greatest effect. The coumarins 3-(1′,1′, dimethyl allyl)-herniarin, auraptene, 8-geranyl-oxy psoralen, isopimpinellin and the flavonoid zapotin were isolated from the extracts. The hexane extract of C. pubescens showed an antidepressant-like activity, which may inspire further studies on developing new antidepressant agents.     

Studies on the Preparation and Biological Activities of 3-(O-Methoxybenzyl)Sydnone Derivatives and 3-(Fluorophenyl)Sydnones

Two new sydnones; 3-(o-methoxybenzyl)sydnone(1) and 3-(o-melhoxybenzyl)-4-morpholinomethylsydnone(2) were synthesized from o-methoxybenzylamine and ethyl bromoacetat in moderate yields. 3-(o-,m-,p-Fluorophenyl)sydnones were prepared from the corresponding fluoroaniline and chloroacetic acid in higher yields with a conventional method. From the biological activity test, 1 shows significant response of coronary dilation test, collagen induced platelet aggregation inhibition, local anesthetic and moderate cardiotropic activity. In addition, 1 also leads to anticonvuls, muscle relaxation and behavior depression. But 2 only shows inhibition of collagen induced platelet aggregation and antiwrithing. 3-(p-Fluorophenyl)sydnone (5) shows significant response of coronary dilation, collagen induced platelet aggregation inhibition, moderate cardiotropic activity, antiwrithing and local anesthetic But 3-(o-Fluorophenyl)sydnone(3) and 3-(m-fluorophenyl)sydnone(4) only show coronary dilation and moderate cardiotropic activity.     

Fractal analysis of pit morphology of Inconel alloy 600 in sulphate,nitrate and bicarbonate ion-containing sodium chloride solution at temperatures of 25–100 °C

Pit morphology of Inconel alloy 600 in sulphate (SO₄ ^2-), nitrate (NO₃ ^-) and bicarbonate (HCO₃ ^-) ion-containing 0.5 M sodium chloride (NaCl) solution was analysed in terms of fractal geometry as functions of solution temperature and anion concentration using the potentiostatic current transient technique, scanning electron microscopy, image analysis and ac-impedance spectroscopy. Potentiostatic current transients revealed that the pitting corrosion is facilitated by the increase in solution temperature, irrespective of anion additives, and that it is hindered by the increase in NO₃ ^- and HCO₃ ^- ion concentration, regardless of solution temperature. Above 60 °C, it was also found that the addition of SO₄ ^2- ions impedes pit initiation, but enhances pit growth. The value of fractal dimension D _f of the pits increased with increasing solution temperature and with decreasing NO₃ ^- and HCO₃ ^- ion concentration. Moreover, the value of D _f increased above 60 °C with increasing SO₄ ^2- ion concentration. This is caused by the increase in the ratio of pit perimeter to pit area, implying the formation of pits with micro-branched shape due to the acceleration of the local attack in the pits. From the decrease of the depression parameter with increasing solution temperature, it is inferred that the roughness of the pits increased with increasing solution temperature. In addition, the depression parameter was found to increase with increasing NO₃ ^- and HCO₃ ^- ion concentration. But, above 60 °C, in the case of SO₄ ^2- ion addition, the depression parameter decreased with increasing SO₄ ^2- ion concentration. From the experimental findings, the three-dimensional pit morphology is discussed in terms of the values of D _f of the pits and the depression parameter, with respect to anion concentration and solution temperature.